Ratchet And Clank return to their home galaxy (revealed to be named the Solana Galaxy) where they face off against Dr. Nefarious, a Mad Scientist and robot supremacist who also happens to be a former foe of Captain Qwark. The two reluctantly track down and team up with the disgraced superhero in order to thwart Dr. Nefarious's scheme to turn everyone in the galaxy into his robotic slaves.

This game contains examples of:

Beware the Nice Ones: An in-game meta example. The Annihilation Nation announcer says that most people know Ratchet as Secret Agent Clank's bumbling chauffeur. Said bumbling chauffeur then goes and blows a ton of crap up in the arena with weapons as big as he is.

Boss Remix: The boss theme for the fight against Courtney Gears is a remix of "Death to Squishies".

Brain Uploading: A cross between this and We Can Rebuild Him is what caused Nefarious to become the robot he is now after a horrible accident at the hands of Qwark while he was still human, though it's never quite explained which is more accurate.

Call Back: The Amoeboids from Ratchet & Clank are revealed to have been an early galactic domination/destruction ploy by Dr. Nefarious (making their appearance then something of a Foreshadowing for him).

Also in the 4th Vidcomic you visit Qwark's training course as Qwark.

Several enemies from the original game and Going Commando make a cameo in the opening cutscene as pieces on their board game.

Changed My Mind, Kid: They find Captain Qwark after he faked his death so he wouldn't have to actually risk his life, and are unable to convince him to continue fighting. Later on, in the final boss battle, he comes dramatically sailing in on his spaceship, pumping rounds into the boss.

Chaos Architecture: Veldin, barring the location where Ratchet's garage is, looks absolutely nothing like it did in the original game, having a completely different level layout and desert like appearance. While the desert like atmosphere could have been an effect of the Tyhrranoid invasion, it still fails to explain how the geography could undergo such a rapid change in the year and a half Ratchet was gone from Veldin.

In the first game small floating islands are encountered, which would give a reason for accelerated change of geography: the ground seen is actually floating and able to move.

Charles Atlas Superpower: One of the vid-comics shows Qwark stowing away on Nefarious' spaceship by clinging onto it for dear life, and survives the six-day space travel by holding his breath the whole trip. While it sounds like something Qwark would embellish, the game Size Matters would retroactively reveal that he could actually do this.

Truth in Television: Surprisingly, it technically is possible to hold your breath in the vacuum of space, but there would be far more hazards in space to put up with alongside it, and it would be incredibly difficult (and obviously, extremely dangerous) and only possible for a very brief period of time, and it would be completely useless (and outright lethal) in the context Qwark pulled it off in.

Courtney Gears appears for the first time when you first win on Annihilation Nation, before you discover her role in Nefarious's plot.

The Tyrrha-guise is only used in a single area, then comes back in the final level, where the Tyrrhanoids are back, and a lot smarter.

On your first visit to the Phoenix you can see areas off to the side of the lift platform with no way to access them, then the ship gets attacked at the end of the game and the lift is destroyed opening up those areas as an alternate route.

Comically Missing the Point: Shows up every now and then. The first instance occurs when Ratchet finds Al using a city's defense system to play a video game. Ratchet asks Al how he could do such a thing, and Al responds by listing the steps he took to hack into the system, instead of answering why he would use an important installation for such an irrelevant activity.

*Cough* Snark *Cough*: The narrator does this at the end of the first Qwark Vid-Comic, the one with the robotic pirate ghosts.

"The exciting, all true, *cough* right *cough* adventures of Captain Qwark continue in Episode 2."

Fan Disservice: Qwark when he's disguised as a maid delivering a pizza to Dr. Nefarious in the third vidcomic. The pic gives you a clear view of his fishnet stockings and undergarments. This happens again later when Qwark disguises himself as a top-heavy woman while calling a Taxi Cab, and again with the Tutu cheat code for the Vid-comics.

For a while, Clank's red eyes and evil grin may look like he might pull this off, himself. Of course, we later learn he is not really Clank.

Fake Ultimate Mook: Despite looking intimidating, King Amoeboids are downright pathetic (and VERY easy to one-hit kill) once your weapons are decently leveled. You can even use the Quack-O-Ray on them for D.I.Y Nightmare Retardant.

Foreshadowing: It's made very clear that Nefarious and Lawrence survived the blast at the end of the game.

Genre Savvy: Upon seeing Nefarious with Clank, Ratchet immediately realizes there's an Evil Twin about, and promptly feels stupid for not picking up on such sooner.

Ratchet: Hey, Clank, look! It's Dr. Nefarious! And that butler guy! And they've got Clank! They're, uh, holding you prisoner. How about that? I guess I should be feeling pretty stupid right now. I don't suppose there's any chance he's the evil Clank?

Some also feel that the Galactic President resembles Bill Clinton (especially his voice).

No Respect Guy: Poor Ratchet. People only see him as the incompetent chauffeur he plays as in "Secret Agent Clank," despite having saved two galaxies in the past. He's also forced to do all the legwork in stopping Dr. Nefarious, and Clank and Quark tend to reap all the credit.

Old Save Bonus: If you import a Ratchet & Clank save, you get the Gadgetron employee discount mentioned in said game (the one that takes two years to kick in). Also, having a Going Commando save with certain guns obtained in it will let you get those guns for free.

Old Shame: In-Universe, the unreleased Vid-Comic 5 is this to Qwark, as it reveals that after beating Dr. Nefarious, he was knocked out by Lawrence and subsequently captured. It was so embarrassing for him that he attempted to end the series at the fourth part.

Orwellian Editor: In-Universe, Qwark attempts this with the Vid-Comic series, either altering or taking out parts where he was less than heroic, going as far as attempting to eliminate the fifth episode entirely.

Peninsula of Power Leveling: The sewers on Aquatos. There are hundreds, if not thousands of ameoboids throughout the level, they're easily dispatched, and they attack in narrow corridors where you can see them coming. This makes it the perfect place to level up weapons.

What Happened to the Mouse?: Dr. Nefarious's plan is to turn every organic lifeform in the galaxy into robots, and he actually succeeds in doing so to Skidd McMarxx and everyone in Metropolis. Later in the game, Al is seen analyzing Skidd and remarking that it may be possible to reverse the process, but it is never really stated whether Al succeeds or not. Granted, Skidd does make a very brief appearance in the cinema at the end of the game, back to his normal self, suggesting Al did cure him and everyone in Metropolis.

Who Writes This Crap?!: The narrator from the vid-comics in the their game, expressing his disbelief on Qwark's supposed "adventures". Considering Qwark wrote the scripts, one can't blame him.

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